The subject of the proposed research is the study of the ontogeny (origins, differentiation pathways and anatomical distributions) and functions of the lymphocytes which comprise the T cell system in the rat. Central to this study is the use of highly specific anti-lymphocyte sera in conjunction with cell fractionation techniques, to identify and isolate developmentally and functionally distinct lymphocyte subpopulations. We have already identified five antigenically distinct subsets of lymphocytes with these techniques. These include: a population of bone marrow lymphocytes which contains the precursors of T cells, B cells and hemopoietic stem cells; 2 populations of thymocytes which correspond to cortical and medullary thymocytes, respectively; and 2 populations of peripheral T cells, one of which is antigenically related to cortical thymocytes, and one to medullary thymocytes. These, and other lymphocyte subpopulations that may be identified, will be studied to determine: 1) the identity of the lymphopoietic stem cells in bone marrow; 2) the developmental relationships between cortical and medullary thymocytes and peripheral T cells; and 3) the functional capabilities of subsets of thymocytes and peripheral T cells. In addition, the subcellular localization of terminal deoxynucleotidyl transferase (TdT) in cortical thymocytes will be determined using monospecific antisera to this unique enzyme. The origin functions and fate of TdT-positive cells will be studied in in vivo and in vitro systems. BIBLIOGRAPHIC REFERENCES: Goldschneider, I. (1975). Antigenic relationship between medullary thymocytes and a subpopulation of peripheral T cells in the rat: Description of a masked antigen. Cell. Immunol. 16:269-284. Barton, R. W., Goldschneider, I. and Bollum, F. J. (1976). The distribution of terminal deoxynucleotidyl transferase (TdT) among subsets of thymocytes in the rat. J. Immunol. 116:462-468.